Patients who suffer from allergies of the immediate type (atopies) have the capacity to make special kinds of allergic antibodies (reagins) upon exposure to certain substances (allergens) towards which they are sensitive. The reagins become strongly attached to certain tissues, particularly those of the epithelium. Following a subsequent exposure to the sensitizing allergenic material, a physical combination occurs between the allergen(s) and their homologous reagins, resulting in allergic manifestations at the sites of reagin-allergen combination. Allergic individuals are also able to produce the so-called "blocking antibodies" of a non-reagin type which are capable of combining with and inactivating the allergen, generally without any undesirable side reactions. Reaginic activity has been attributed to Immunoglobulin E (IgE) and "blocking" activity mainly to IgG in the serum and IgA in secretions.
The term "allergic" as used here will be restricted to defining allergies of the immediate (atopic) type.
It has long been the clinical practice to inject an allergic patient with gradually increasing doses of aqueous extracts containing the allergenic material(s) toward which the patient is sensitive. The rationale behind this treatment is primarily to build up the concentration of protective blocking antibody in the serum (and other body fluids) to a level where it can effectively compete with the tissue-fixed reagin for allergen which enters the body, thereby inhibiting the allergic reactions. In certain cases, this therapy has also been found to suppress the production of reagins and to decrease the cellular responsiveness toward the injected allergens. The immunizing doses of the allergenic extract must be increased very gradually during the course of the treatment in order to minimize the risk of a general allergic (anaphylactic) response in the patient.
The main disadvantages of this immunotherapy are: (i) repeated injections are required over many weeks, (ii) the treatment is seldom completely effective in alleviating the allergic syndrome and (iii) the risk of general anaphylactic reaction is always present at each stage of the treatment.
The original therapy has, therefore, been modified with the aim of overcoming these disadvantages. More recent forms of treatment include immunizing the patient with either a water-in-oil emulsion of the allergenic extract or by including a slow release adjuvant such as an alginate with an extract of the allergenic material. Such methods have not proved to be entirely satisfactory due to the occurrence of some anaphylactic and some toxic reactions in the patient or to the failure of these preparations to be completely effective clinically.
Several workers have treated allergenic materials chemically or physically in an attempt to reduce substantially their allergenic properties, but retain their capacity to protect an allergic individual against the native allergen. Immunotherapy of allergic individuals using such modified allergens would, it was hoped, retain the desired immunizing properties of the native allergen, primarily in the sense that blocking antibody against the native allergen would be produced in significant quantity. Furthermore, the reduced allergenicity of such modified materials would permit the use of greatly increased doses of immunizing material and, thus, greatly enhance the quantity of protective blocking antibody produced.
It has now been found that, by a new process employing formaldehyde solution, the great majority of allergen-containing substances may be so modified that the said disadvantages of the native allergens with regard to their use in immunotherapy are overcome. Hereinafter, any allergen-containing substance will be referred to simply as an allergen, although it is recognized that not all components of an allergen-containing substance are necessarily allergenic. In referring to the new formaldehyde treatment the terms "formalinized" and "formalinization" will be restricted to describing the treatment of amino-containing allergenic materials with formaldehyde where definite chemical reaction takes place between amino groups and formaldehyde, involving the establishment of inter- or intramolecular methylene bridge linkages between or within the allergen molecules themselves or between allergen and other reactive molecules present in the reaction mixture.